DO ANDROGENS PREDICT CARDIOVASCULAR RISK INCLUDING CARDIOTROPHIN-1 LEVELS in PATIENTS WITH OBESE and LEAN POLYCYSTIC OVARY SYNDROME.

Introduction: We aimed to investigate Cardiotrophin-1 (CT-1) levels along with other markers of cardiovascular disease and the association of androgen levels with these parameters in both lean and overweight or obese PCOS patients. Material and Methods: The study included 90 overweight or obese PCOS patients with metabolic syndrome (MS) and 80 lean PCOS patients without MS. The control group consisted of 140 healthy females. Anthropometric measurements, plasma glucose, insulin, lipid and hormone profile, homocysteine, hs-CRP, CT-1 levels and carotid-IMT were evaluated in all study subjects. Results: Fasting insulin, HOMA values were significantly higher in obese PCOS patients. Total testosteron levels were higher in both PCOS groups with respect to both controls. Serum homocysteine, hs-CRP, CT-1 and carotid-IMT values were significantly higher in both PCOS groups compared to controls (p=0.001, pCIMT: 0.005). CT-1 was positively correlated with insulin, HOMA, total testosterone, homocysteine, hs-CRP and carotid IMT. After multiple regression analysis, CT-1 was significantly positively correlated with total testosterone, hs-CRP and carotid IMT. Conclusions: CT-1 was associated with other cardiovascular risk markers and its use as a cardiovascular risk marker might be suggested. Cardiovascular risk was increased even in lean PCOS patients without MS and it might be associated with elevated androgen levels.

A systematic review: Role of systemic therapy on treatment and prevention of brain metastasis in renal cell carcinoma.

AIM: To define the inclusion/exclusion status of patients with brain metastasis in phase-III clinical trials and the effect of systemic therapies in metastatic renal cell cancer patients with brain metastasis. METHODS: "kidney neoplasms"[MeSH Terms] OR ("kidney"[All Fields] AND "neoplasms"[All Fields]) OR "kidney neoplasms"[All Fields] OR ("kidney"[All Fields] AND "cancer"[All Fields]) OR "kidney cancer"[All Fields] AND "brain metastasis" were used for searching "PubMed" electronic database and "clinicaltrials.gov" website. RESULTS: Five of 19 landmark phase-III clinical trials included patients with stable or asymptomatic brain metastasis and there was no data about outcomes of brain metastasis. The effect of systemic therapy on prevention of brain metastasis in renal cell cancer was evaluated in four studies. Two studies showed that the incidence of brain metastasis decreased, while the other two studies showed no effect of antiangiogenic agents on the prevention of brain metastasis in patients with renal cell cancer. There were 10 trials regarding systemic therapy of renal cell cancer brain metastasis. The overall response rate improved through a combination of targeted therapies and local treatment. The results of the trials studying the effect of tyrosine kinase inhibitors without local treatment were controversial. None of the ongoing clinical trials included patients with active brain metastasis. CONCLUSION: In metastatic renal cell cancer patients with brain metastasis, the overall response rate improved with the combination of targeted agents and local treatment. Further trials are needed to evaluate the effect of systemic treatment on the prevention or treatment of brain metastasis in patients with renal cell cancer.

Prognostic factors for survival in patients with mucosal and ocular melanoma treated with ipilimumab: Turkish Oncology Group study.

OBJECTIVE: To evaluate prognostic factors associated with the use of ipilimumab in patients with mucosal and uveal melanoma. METHODS: In this multicenter, retrospective study, 31 patients with uveal and mucosal melanoma diagnosed between 2010 and 2017 were enrolled. Patients' characteristics, metastatic disease sites, treatment before ipilimumab therapy, performance status, hemoglobin, lactate dehydrogenase levels, B-RAF and c-kit mutation status, toxicity, and survival data were assessed for patients with mucosal and uveal melanoma. SPSS version 17 was used for statistical analysis. Kaplan-Meier method was used for survival analysis. The log-rank test was used for univariate analyses. The Cox regression analysis was used to test the association between multivariate variables and survival. The p-value of less than 0.05 was considered statistically significant. RESULTS: Twenty patients had uveal and eleven patients had mucosal melanoma. The median overall survival was seven months (95% confidence interval: 1.1-12.7). In univariate analysis, while bone metastasis, anemia, high lactate dehydrogenase level, and more metastatic sites were associated with lower overall survival, better treatment response and administration of ipilimumab in first or second lines were associated with favorable overall survival. In multivariate analysis, only treatment response status and administration of ipilimumab in first or second lines were found to be significant as independent prognostic factors for survival. CONCLUSION: Ipilimumab therapy may be associated with increased survival, but this retrospective small N study makes that hard to definitely conclude.

Prognostic factors for survival in patients with metastatic malign melanoma treated with ipilimumab: Turkish Oncology Group study.

PURPOSE: Studies in the last decade show survival improvement with checkpoint blocker therapy in patients with metastatic malign melanoma. Our purpose was to define the efficacy of ipilimumab according to the patient's baseline characteristics including absolute lymphocytes count. METHODS: We collected the data of 97 patients with advanced malign melanoma treated with ipilimumab (3 mg/kg, q3w) retrospectively. Log-rank test was used to analyze the univariate effects of patient's characteristics (age, gender, metastatic sites, ECOG PS, type of melanoma, lactic dehydrogenase levels, anemia, lymphocytes (L), neutrophils (N), N/L ratio), c-kit and BRAF status. Survival analyses were estimated with Kaplan-Meier method. Cox regression analysis was used to assess the possible factors identified with log-rank test. RESULTS: The median age was 58, and 58% were male and 90% of patients had at least one prior systemic therapy. The median survival was 9.7 months for all patients; and the 12- and 24-month survival rates were 43% and 19%, respectively. Absolute lymphocytes count, lactic dehydrogenase level, bone metastasis, the number of metastatic sites, and RECIST response were significantly related to survival. After Cox regression analysis, RECIST response (complete or partial response), absolute lymphocytes count (more than 1500/mm3) and the number of metastatic sites (less than three sites) remained as significant independent prognostic factors for longer survival. CONCLUSION: Ipilimumab improved survival of patients with metastatic malign melanoma. However, patients with fewer metastatic sites and higher absolute lymphocytes count have a significantly better benefit. To determine if these markers could be used to direct patient therapy, further validation analysis is needed.

Correlation between Bethatrophin and 25(OH)D Concentrations in a Group of Subjects With Normal and Impaired Glucose Metabolism.

Aim: Inducing beta cell replication is a potential therapeutic approach for the treatment of diabetes mellitus. Recently betatrophin was suggested as a novel stimulator of beta cell proliferation in mice but its role in humans remains to be established. We aimed to investigate betatrophin concentration and its association with metabolic parameters in a group of individuals with normal glucose tolerance, pre-diabetes and diabetes mellitus who had not been previously treated. Methods: A total of 72 subjects were recruited for this cross sectional study: 23 subjects with normal glucose tolerance (NGT), 22 subjects with prediabetes, and 27 subjects with diabetes mellitus (DM). Circulating betatrophin concentration, 75 g oral glucose tolerance test, fasting insulin, glycosylated hemoglobin, 25hydroxy vitamin D and HOMA IR were measured. Results: The difference in betatrophin values did not reach statistical significance between the 3 groups [NGT:206 (176-297)pg/mL, Prediabetes:232 (181-254)pg/mL, DM:245 (205-526)pg/mL, p=0.078]. Betatrophin was negatively significantly correlated with BMI and positively significantly correlated with 25(OH)vitD (p=0.043 and p=0.001 respectively). Multivariate linear regression showed that 25(OH) vitD (ß=0.440 p=0.001) and fasting glucose (ß=0.003 p=0.038) were variables associated with betatrophin concentration (R2=0.251). Conclusions: In a group of subjects ranging from those with normal glucose tolerance to newly diagnosed diabetes, we found that 25(OH)D and fasting glucose were factors associated with serum betatrophin concentration.

JAK2 V617F MUTATION SCANNING IN PATIENTS WITH ADRENAL INCIDENTALOMA.

OBJECTIVE: Adrenal incidentaloma are lesions which are stated incidentally by imaging methods when there is no suspicion of any disease in adrenal gland. Inappropriate Jak2 signaling causes some solid and hematological malignancies. But the Jak2 mutation has not been previously evaluated with regard to adrenal tumors. In this study, we aimed to positivity of the Jak2 mutation in patients with non functioning adrenal incidentaloma (NFAI). METHODS: 45 (38 female-7 male) patients, who were followed due to NFAI at Tepecik Training and Research Hospital, Department of Endocrinology and Internal Medicine between February 2014 and March 2015, and 45 (31 female-14 male) healthy controls were included in the study. RESULTS: The average age was 54.02±11.7 years and 38 patients were female, 7 were men. All patients underwent the following analyses for excluding a functioning adrenal mass, overnight dexamethasone suppression test, 24 hour urinary metanephrine and normetanephrine, plasma aldosterone/ renin activity ratio. Jak2 mutation of the patients who were diagnosed as NFAI was all negative. CONCLUSION: We could not identify the JAK2 gene mutation positivity in any sample. Since other possible mechanisms may throw fresh light on the etiology of adrenal incidentaloma, further clinical studies are needed on this subject.

THE EFFECT OF EXENATIDE THERAPY IN PREVIOUSLY INSULIN-TREATED TYPE 2 DIABETIC PATIENTS.

OBJECTIVE: To evaluate the effect of multiple daily injection (MDI) treatment replaced by Exenatide BID as compared with continuation of MDI. PATIENTS AND METHODS: A total of 140 patients with type 2 diabetes, taking metformin and multiple daily insulin injections, were randomized to exenatide or insulin group that continued their insulin treatment. Patients were followed-up for 16 weeks. Blood glucose profiles, BMI, waist circumference, HbA1C, serum lipids and side effects were assesssed at weeks 0,12 and 16. RESULTS: There were no significant differences between the two groups with respect to baseline parameters. Glycemic control was similar between the two groups. The mean changes in HbA1C in exenatide group were -0.66±0.63% and in insulin group -0.74±0.92 % (p=0.594). In exenatide group, 59.6 % of patients and in insulin group 85.71 % of patients had maintained or improved glycemic control at the end of the study. In insulin group, insulin requirement increased 5.86 ± 4.46 units/day. Body weight and waist circumference decreased significantly in exenatide treatment group with respect to insulin group (p<0.001). CONCLUSIONS: Substituting exenatide for insulin might be an option in insulin-treated, type 2 diabetic patients having obesity, and poor glycemic control. However, patients with longer duration of diabetes and insulin treatment and with lower C-peptide levels might not benefit from exenatide therapy.

MEAN PLATELET VOLUME AND PLATELET FUNCTION ANALYSIS IN ACROMEGALIC PATIENTS BEFORE AND AFTER TREATMENT.

OBJECTIVE: Mean platelet volume (MPV) and platelet function analysis have been studied before in acromegaly, but the effect of treatment on both parameters has not been evaluated. We aimed to investigate MPV and platelet function analysis in acromegalic patients after six-months of treatment. METHODS: Forty patients with active acromegaly and 36 healthy subjects were included in the study. Plasma glucose and lipids, fibrinogen, GH, IGF-1 levels, MPV and platelet function analysis were measured. All patients with acromegaly were re-evaluated six months after treatment. RESULTS: Fasting blood glucose (FBG), GH, IGF-1, fibrinogen levels and MPV values were significantly higher in acromegalic group compared with the control. Platelet function was enhanced significantly (pcol-ADP: 0.002, pcolepinephrine: 0.002). After 6 months of treatment FBG, serum GH, IGF-1, fibrinogen and MPV decreased and collagen/ADP- and collagen/epinephrine-closure times (CT) were increased. Acromegalic patients that were in remission with long-acting SSA after surgery had significantly higher fibrinogen levels and MPV and decreased collagen/epinephrine-CT with respect to the controls (pfibrinogen: 0.001, pMPV: 0.026, pcol-epinephrine: 0.037). CONCLUSION: Acromegaly was associated with increased MPV and enhanced platelet activity. Although growth hormone hypersecretion was controlled by surgery and medical treatment, these parameters did not improve - indicating a still increased risk for cardiovascular events.

IS SUBCLINICAL HYPOTHYROIDISM IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME ASSOCIATED WITH BMI?

OBJECTIVE: To investigate the impact of body weight on the subclinical hypothyroidism observed in patients with PCOS. METHODS: The study included 95 normal weight (Group-1) and 122 overweight or obese women (Group-2) with PCOS. The control group consisted of age and BMI matched healthy individuals and grouped as normal weight (n: 66, Group-3) and overweight or obese (n: 65, Group-4. Women with chronic disease such as overt thyroid dysfunction, late-onset adrenal hyperplasia, and diabetes were excluded from the study. Plasma glucose and lipid profile, thyroid hormones, insulin, FSH, LH, total testosterone, estradiol, progesterone and DHEA-S were measured. RESULTS: While fasting glucose was similar, insulin and HOMA-IR were higher in Group-2 and Group-4 (p: 0.001). The groups were similar with respect to FSH, Estradiol, prolactine, DHEAS. While total testosterone and LH levels were higher (ptestosterone: 0,009), progesterone was lower in both PCOS groups (pprogesterone: 0.041). Free T3, free T4, thyroid antibodies were similar between the groups, but the prevalence of subclinical hypothyroidism was greater in Group-2 and -4 than in Group-1 and -3 (p: 0.044). TSH was only correlated with BMI (r: 0.122, p: 0.02). CONCLUSION: The increased prevalence of subclinical hypothyroidism in women with PCOS might be the result of increased BMI.

Antrochoanal polyposis: analysis of 34 cases.

An antrochoanal polyp (ACP) is a benign polypoid lesion originating from the maxillary sinus and extending to the choana. The objective of our study is to assess etiological and associated features of ACPs, and outcome following surgical treatment. Thirty-four patients who had received surgical treatment for ACPs were followed for 35 ± 17.7 months. Factors including patient age, gender, history of allergic rhinitis, chronic sinusitis, nasal septal deviation, turbinate hypertrophy, concha bullosa, accessory ostia, as well as the origin of the polyp, the surgical technique used and any recurrence, were evaluated. Overall, there were 12 females and 22 males. Mean age was 24.94 ± 8.08. Septal deviation was present in 50 %, turbinate hypertrophy in 32.3 %, concha bullosa in 17.6 %, mucous retention cyst in 32.3 %, allergic rhinitis in 44.11 %, and chronic sinusitis in 20.5 %. An accessory ostia was observed in 97.05 %. The functional endoscopic sinus surgery (FESS) approach was used in 31 cases, and three cases had combined FESS and Caldwell Luc procedures. The mean follow-up time was 35.8 ± 17.7 months. Two cases, who had been treated with FESS alone, experienced a recurrence. In conclusion, the commonest predisposing factors for ACPs are chronic inflammatory pathologies such as chronic sinusitis and allergic rhinitis. ACP left the maxillary sinus via an accessory ostium in 97.5 % of the cases. The FESS procedure is a safe and reliable method, and can be combined with the Caldwell Luc procedure when the origin of the maxillary component cannot be properly cleaned. In order to prevent recurrence, total extirpation of the maxillary component is essential.

Thermal welding technique versus cold dissection for adult tonsillectomy.

OBJECTIVES: To compare the thermal welding technique (TWT) with cold dissection (CD) for adult tonsillectomy. METHODOLOGY: A prospective, double-blind, non-randomised study was planned for 20 adult patients undergoing tonsillectomy; a total of 16 patients were included for evaluation. In all patients, the right tonsil was removed by TWT, the left tonsil by CD. Indications included chronic tonsillitis with or without upper airway obstruction. Patients with peritonsillar abscess history or bleeding disorders were excluded from analysis. Age, gender, dissection and hemostasis time, intra-operative hemostasis method, post-operative pain using a visual analogue scale, and extent of healing of the tonsillar fossa on the tenth post-operative day were evaluated. RESULTS: TWT was significantly superior to CD with regard to intra-operative hemostasis (p = 0.029). There were statistically significant differences between the two techniques in a post-operative pain score (p = 0.001). There were no statistically significant differences between the two techniques in dissection and hemostasis time (p = 0.321), nor in the healing of the tonsillar fossae on the tenth day of the surgery (p = 0.285). CONCLUSION: Compared with CD, TWT provides sufficient hemostasis and lower post-operative pain, as assessed in a limited number of adult tonsillectomy cases.

Antibiotic resistance patterns of coagulase-negative staphylococcus strains isolated from blood cultures of septicemic patients in Turkey.

The aim of this study is to determine antibiotic resistance patterns and slime production characteristics of coagulase-negative Staphylococci (CoNS) caused nosocomial bacteremia. A total of 200 CoNS strains were isolated from blood samples of patients with true bacteremia who were hospitalized in intensive care units and in other departments of Istanbul University Cerrahpasa Medical Hospital between 1999 and 2006. Among 200 CoNS isolates, Staphylococcus epidermidis was the most prevalent species (87) followed by Staphylococcus haemolyticus (23), Staphylococcus hominis (19), Staphylococcus lugdunensis (18), Staphylococcus capitis (15), Staphylococcus xylosus (10), Staphylococcus warneri (8), Staphylococcus saprophyticus (5), Staphylococcus lentus (5), Staphylococcus simulans (4), Staphylococcus chromogenes (3), Staphylococcus cohnii (1), Staphylococcus schleiferi (1), and Staphylococcus auricularis (1). Resistance to methicillin was detected in 67.5% of CoNS isolates. Methicillin-resistant CoNS strains were determined to be more resistant to antibiotics than methicillin-susceptible CoNS strains. Resistance rates of methicillin-resistant and methicillin-susceptible CoNS strains to the antibacterial agents, respectively, were as follows: gentamicin 90% and 17%, erythromycin 80% and 37%, clindamycin 72% and 18%, trimethoprim-sulfamethoxazole 68% and 38%, ciprofloxacin 67% and 23%, tetracycline 60% and 45%, chloramphenicol 56% and 13% and fusidic acid 25% and 15%. None of the strains were resistant to vancomycin and teicoplanin. Slime production was detected in 86 of 200 CoNS strains. Resistance to methicillin was found in 81% of slime-positive and in 57% of slime-negative strains. Our results indicated that there is a high level of resistance to widely used agents in causative methicillin-resistant CoNS strains. However fusidic acid has the smallest resistance ratio, with the exception of glycopeptides. Additionally, most S. epidermidis strains were slime-positive, with statistically significant (p<0.001) association between methicillin resistance and slime production.

Resolution in partially accomodative esotropia during occlusion treatment for amblyopia.

PURPOSE: To evaluate alignment changes in partially accommodative esotropia during occlusion treatment for amblyopia. METHOD: Changes at the deviation angles of 63 partially accommodative esotropia patients, who had occlusion treatment for amblyopia, were evaluated retrospectively. RESULTS: Mean deviation angle at the start of therapy without glasses was 45 PD (10-90 PD) and became 27 PD (5-70 PD) after at least 2 months with glasses. During 12 (2-36) months of occlusion period, mean manifest deviation angle with glasses decreased to 11 PD (0-50) (P < 0.001) and amblyopia resolved in 71.5% of the cases. After termination of amblyopia treatment 24 (38%) cases had surgery for the residual deviation but if we had planned surgery before amblyopia treatment, 81% of the patients would have had surgery. DISCUSSION: Should amblyopia be treated initially or should we operate first in patients with strabismus and amblyopia together? Our research suggests that we should not hurry to operate in high hypermetropic partially accommodative cases, which have amblyopia and a long-term history of strabismus. Initial amblyopia treatment in these cases allows time for resolution of the nonaccomodative component in strabismus and can significantly decrease the necessity for surgery.

Parasites in nosocomial diarrhoea: are they underestimated?

Nosocomial diarrhoea, defined as diarrhoea occurring more than 72 h after hospital admission, is reported to account for <1% of endemic nosocomial infections and 17% of epidemic nosocomial infections. The yield of diagnoses from stool cultures in nosocomial diarrhoea is low, and information regarding the role of parasites is limited. We conducted a study to determine the responsible bacterial and parasitological pathogens from nosocomial diarrhoea cases in our 2000-bed tertiary care facility over a 16-month period. Of 226 patients, Clostridium difficile toxins A or B were present in 5.5%, giardia cysts and/or trophozoites in 4.4%, Blastocytis hominis in 4.4% and Cryptosporidium sp. in 0.5% of samples. In conclusion, parasites should be sought in nosocomial diarrhoea in endemic areas.

Fine-needle aspiration as a diagnostic tool for recurrent tonsillitis.

Acute tonsillitis is a common childhood disease, but repeated antibiotic treatment may fail, leading to tonsillectomy. Superficial swab cultures do not sufficiently represent the core bacteria present, but fine-needle aspiration may be a promising diagnostic method. We evaluated 58 patients undergoing tonsillectomy, and took superficial and core swabs, and fine-needle aspirations. Staphylococcus aureus was the most common bacterial pathogen identified, present in 26 out of 50 (52%) positive core cultures, followed by Haemophilus influenza in 13 positive core cultures (26%), and group A beta-haemolytic streptococci in 10 positive core cultures (20%). Fine-needle aspiration detected 33 out of 50 positive core cultures (66%), whereas superficial swab culture detected 18 of 50 (36%); the difference being statistically significant. All pathogens detected by superficial swabs and fine-needle aspiration were detected in core cultures. The sensitivity and specificity of fine-needle aspiration were 66% and 100%, respectively, compared with 36% and 100% for superficial swabs. Fine-needle aspiration is therefore a promising method for detecting core bacteria in patients with recurrent tonsillitis.

Urinary nephrocalcin excretion in children with urolithiasis.

The aim of this study was to investigate the role of nephrocalcin in childhood urolithiasis. Forty-one patients with urinary stones and 25 age- and sex-matched healthy controls were admitted to the study. Blood and timed urine samples were taken from both patient and control groups for biochemical analysis. Serum and urine creatinine (Cr) and urinary nephrocalcin (NC) were measured. NC excretion was expressed as a NC/Cr (mg/g) ratio. NC-PreA/Cr and NC-D/Cr ratios were found to be significantly higher in patients than in the control group. No statistically significant differences were found in NC-A/Cr, NC-B/Cr, NC-C/Cr ratios between the patient and control groups. The high NC-PreA/Cr ratio (p = 0.012) observed in stone-forming patients indicates that this ratio may also be an important stimulatory factor for urinary stone disease.

Environmental contamination during a carbapenem-resistant Acinetobacter baumannii outbreak in an intensive care unit.

During a three-month period in 1999, 25 strains of carbapenem resistant Acinetobacter baumannii were isolated from 12 of 170 hospitalized intensive care unit (ICU) patients, of which 16 were considered to be clinically significant. These strains were indistinguishable by biotyping and antibiograms, but genotyping was not performed. Appropriate antibiotic treatment, isolation precautions, and infection control education of the staff failed to halt the outbreak. Environmental contamination was therefore investigated, and A. baumannii was found out in 22 (39.3%) of 56 environmental samples obtained by swabbing. Different antibiotic sensitivity patterns were obtained in the majority of these isolates, but four (7.1%) of the strains were found to have the same sensitivity pattern as the strain causing the outbreak. As a result the ICU was closed, equipment and the environment cleaned, with hypochlorite and terminal disinfection carried out. No bacteria were grown on repeat environmental cultures. Environmental contamination has an important reservoir role in outbreaks of A. baumannii in ICUs and must be eradicated in order to overcome such outbreaks.